1. Field of the Invention
This invention resides in the field of process chemistry for the N-alkylation of pyridinealdoximes. In particular, this invention addresses processes for the preparation of intermediates for the synthesis of asymmetrical dipyridinomethyl ethers.
2. Description of the Prior Art
The bis-quaternary salts of certain dipyridinomethyl ethers are known to be effective antidotes for toxic agents that are known in the military as nerve gases as well as for certain insecticides. These antidotes are thus useful to the military, the agricultural industry, and the home gardener, and in general any location or application where there is a risk of exposure to the toxic agents.
The most potent of the antidotes in this class are those with asymmetrical structures, i.e., those in which one or more substituents are present on one of the two pyridine rings and not the other, or the substituent(s) on one of the two pyridine rings differ in either structure or position from those on the other. Unfortunately, antidotes with asymmetrical structures are difficult to manufacture, with known synthesis routes tending to produce low yields and high levels of undesired. An illustration of the difficulty is found in U.S. Pat. No. 5,130,438 (Hsiao, L. Y. Y, et al., Jul. 14, 1992, entitled “Bis-Methylene Ether Pyridinium Compound Preparation”). The product mixtures in this patent include the desired asymmetrical ether together with symmetrical ethers and quaternary salts of the pyridinium compounds that are used as starting materials. One of the most potent compounds disclosed in the patent is 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino)-2-oxapropane (commonly known as “HI-6”), shown as both the dichloride and dimethanesulfonate salts. This compound is only one of four reaction products in the product mixture, however, and recovery of the desired compound requires a lengthy isolation procedure involving multiple recrystallizations and resulting in a low yield. Other disclosures of potential relevance to this invention are U.S. Pat. No. 3,773,775 (Hagedorn, I., Nov. 20, 1973, entitled “Bis-Quaternary Pyridinium Salts”) and U.S. Pat. No. 3,852,294 (Hagedorn, I., Dec. 3, 1974, entitled “Bis-Quaternary Pyridinium Salts”). All patents and other literature cited in this specification is hereby incorporated herein by reference.